Background

Acute cholecystitis in the presence of bacteria-containing bile may progress to suppurative infection in which the gallbladder fills with purulent material, a condition referred to as empyema of the gallbladder. (The underlying cause of cholecystitis involves obstruction of the cystic duct, which causes the buildup of infected fluid.) Systemic antibiotics and urgent drainage or resection are required to reduce the incidence of complications and to avoid or treat associated sepsis.

Pathophysiology

In the bacterially contaminated gallbladder, the stagnation and marked inflammation associated with acute cholecystitis fills the gallbladder lumen with exudative material principally comprised of frank pus. This process may be associated with calculous cholecystitis, acalculous cholecystitis, or carcinoma of the gallbladder. Left untreated, generalized sepsis ensues, with progression in the gallbladder to patchy gangrene, microperforation, macroperforation, or, rarely, cholecystoduodenal fistula. Patients at increased risk for cholecystitis include those with diabetes, immunosuppression, obesity, or hemoglobinopathies.

Etiology

The most frequent etiology of empyema of the gallbladder is unresolved acute calculous cholecystitis in the face of contaminated bile. The most frequently isolated organisms include Escherichia coli, Klebsiella pneumoniae, Streptococcus faecalis, and anaerobes, including Bacteroides and Clostridia species. Suppurative inflammation ensues, tightly filling the gallbladder with purulent debris. Localized or free perforation occurs if drainage or resection is not performed at this juncture. Generalized sepsis frequently accompanies this progression.

A similar pattern is infrequently observed in association with acute acalculous cholecystitis. Rarely, obstruction of the distal common bile duct may result in pus formation within the extrahepatic biliary tree, which can then decompress into the gallbladder. This distends and infects that organ, with ensuing empyema.

Prognosis

If treated early, otherwise healthy patients have a full recovery and return to normal activity.

In patients of advanced age, those who are immunocompromised, or those with significant comorbid conditions (including patients with advanced diabetes mellitus, in whom the condition is more prevalent), the development of empyema of the gallbladder and the resultant sepsis constitute a serious life-threatening event.[1]

Mortality/morbidity

The rate of laparoscopic cholecystectomy procedures converted to an open procedure is significantly higher in patients with empyema of the gallbladder. The postoperative complication rate (regardless of approach) for empyema of the gallbladder is 10-20% and includes wound infection, bleeding, subhepatic abscess, cystic stump leak, common bile duct injury, and systemic complications, including acute renal failure and/or respiratory insufficiency associated with sepsis.

Progression to death is unusual in otherwise healthy individuals but may occur in patients of advanced age, in patients with compromised immunity, or in individuals with significant comorbid conditions.

Complications

The major complications associated with empyema of the gallbladder are localized or free perforation and/or generalized sepsis.

History

The clinical history of a patient with empyema of the gallbladder is similar to that of a patient with acute cholecystitis (from which the empyema derives). As the disease progresses, severe pain and associated high fever, chills, and even rigors may be reported. Patients with diabetes or immunosuppression may exhibit few signs and symptoms.

Physical Examination

Patients with an early empyema of the gallbladder often present no differently than any patient with acute cholecystitis, with symptoms that include fever (temperature, >101°F), stable blood pressure, and mild tachycardia. However, if localized or free perforation has occurred and/or the patient has generalized sepsis, fevers (temperature, 103°F), chills and/or rigors, and confusion may be observed in association with hypotension and severe tachycardia.

Early in the disease process, abdominal examination findings are similar to those of patients with acute cholecystitis, with mild-to-moderate tenderness in the right upper abdomen and a positive Murphy sign (ie, arrest of inspiration as the gallbladder descends to touch a hand previously placed deep in the mid right abdomen).

As the disease progresses, empyema of the gallbladder may be associated with a palpable distended gallbladder that is markedly tender on even superficial palpation.

Persistent and even increasing leukocytosis at levels greater than 15,000/dL (with a left shift on differential) despite appropriate antibiotic therapy is characteristic of empyema of the gallbladder. However, this scenario may occur in association with gangrenous cholecystitis and with several other differential diagnoses.

When arising from complicated acute cholecystitis, liver chemistry findings associated with empyema of the gallbladder are usually within reference ranges, which helps differentiate this condition from empyema of the gallbladder and/or cholangitis secondary to distal biliary tract obstruction. One exception is empyema of the gallbladder in which the enlarged "penile" gallbladder compresses the common/hepatic bile ducts (Mirizzi syndrome), giving rise to mildly elevated alkaline phosphatase and bilirubin levels.

Imaging Studies

Ultrasonography of the gallbladder is indicated in presumed empyema of the gallbladder. The finding of an enlarged, distended gallbladder and associated pericholecystic fluid points to an acute inflammatory process involving the gallbladder. Although suggestive, this does not adequately differentiate uncomplicated acute cholecystitis from the complication with empyema and/or gangrene. Most importantly, it contraindicates further conservative management and signals the need for prompt intervention.

Although ultrasonography is the preferred examination for probable cases of empyema, the condition is frequently discovered on computed tomography (CT) scans performed with other conditions on the differential diagnosis in mind.

On diffusion-weighted (DWI) magnetic resonance imaging (MRI), diffusion restriction in non-neoplastic lesions sometimes provides additional information that can help to establish a correct diagnosis in patients for whom conventional images have yielded equivocal findings. DWI may help to differentiate gallbladder empyema from dense bile or sludge in the gallbladder.[2]

Medical Care

When empyema of the gallbladder is considered, urgent consultation with gastroenterologists and surgeons is essential.

Intravenous antibiotic therapy is an adjunct to urgent decompression and/or resection of the gallbladder when empyema is likely. The choice of antibiotic is based on the organisms presumed to be involved (see Etiology). Early in the course of the disease, good results are achieved with the adjuvant administration of a second-generation cephalosporin. In more advanced cases associated with perforation and/or generalized sepsis, broader spectrum coverage with piperacillin tazobactam is advised.

Antibiotic coverage is modified by culture results (as soon as available) and the known bacterial resistance encountered in the local hospital setting.

Urgent decompression is the goal of therapy for empyema of the gallbladder. In patients who are hemodynamically unstable or in individuals in whom surgery is contraindicated because of significant comorbid conditions, transhepatic drainage of the gallbladder under radiologic guidance may serve as a temporizing or final procedure. Although rapid and marked improvement in the patient's condition usually follows, complete resolution without further septic complication (mandating further intervention) is unpredictable.[3]

Surgical Care

Surgical decompression and resection of the affected gallbladder is the criterion standard of therapy. An advanced laparoscopic surgeon may treat empyema of the gallbladder (without significant gangrenous changes or perforation) with a laparoscopic procedure.[4] Initial decompression may be accomplished under radiographic guidance immediately before the procedure or via intraoperative, laparoscopically guided needle drainage, which allows for more facile manipulation of the gallbladder during the cholecystectomy portion of the procedure.

The conversion-to-open and complication rates reported in the literature for laparoscopic treatment of empyema vary widely. However, they are all significantly higher than the comparative rates reported in the same studies for laparoscopic treatment of uncomplicated acute cholecystitis. Laparoscopic subtotal cholecystectomy is acceptable only if the encountered pericholecystic inflammation is so severe as to preclude safe dissection via either a laparoscopic procedure or an open procedure.[5]

Importantly, the complications are related to the advanced disease process and not to the approach. In skilled hands, no increase is observed in the incidence of laparoscopic surgical misadventure with empyema of the gallbladder. Thus, despite the higher incidence of conversion to an open procedure (40-80%), it is quite reasonable to initially proceed with a laparoscopic procedure.

Following surgical decompression and resection of the gallbladder with empyema, intravenous antibiotic therapy is maintained until fever resolves and the white blood cell count returns to normal. Discharge home, on oral antibiotic therapy, is guided by the results of intraoperative bile cultures.

Medication Summary

Class Summary

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting. Base selection of antibiotics on blood culture sensitivity whenever feasible. Indicated as an adjunct to decompression/resection of the gallbladder with empyema.

Cefuroxime (Ceftin, Zinacef)

Clinical Context:
Binds to penicillin-binding proteins and inhibits final transpeptidation step of peptidoglycan synthesis, resulting in cell-wall death; resists degradation by beta-lactamase; proper dosing and appropriate route of administration are determined by condition of patient, severity of infection, and susceptibility of microorganism.

Piperacillin/tazobactam (Zosyn)

Clinical Context:
Antipseudomonal penicillin plus beta-lactamase inhibitor; inhibits biosynthesis of cell wall mucopeptide synthesis by binding to 1 or more of the penicillin-binding proteins and is effective during active-multiplication stage.